ErbB4 promotes malignant peripheral nerve sheath tumor pathogenesis via Ras-independent mechanisms.

ABSTRACT:

Background

We have found that erbB receptor tyrosine kinases drive Ras hyperactivation and growth in NF1-null malignant peripheral nerve sheath tumors (MPNSTs). However, MPNSTs variably express multiple erbB receptors with distinct functional characteristics and it is not clear which of these receptors drive MPNST pathogenesis. Here, we test the hypothesis that altered erbB4 expression promotes MPNST pathogenesis by uniquely activating key cytoplasmic signaling cascades.

Methods

ErbB4 expression was assessed using immunohistochemistry, immunocytochemistry, immunoblotting and real-time PCR. To define erbB4 functions, we generated mice that develop MPNSTs with floxed Erbb4 alleles (P₀-GGFβ3;Trp53^+/-;Erbb4^flox/flox mice) and ablated Erbb4 in the

SUBMITTER: Longo JF 

PROVIDER: S-EPMC6621970 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature